Activation and Regulation of NLR Immune Receptor Networks

Abstract

Plants have many types of immune receptors that recognize diverse pathogen molecules and activate the innate immune system. The intracellular immune receptor family of nucleotide-binding domain leucine-rich repeat–containing proteins (NLRs) perceive translocated pathogen effector proteins and execute a robust immune response, including programmed cell death. Many plant NLRs have functionally specialized to sense pathogen effectors (sensor NLRs) or to execute immune signalling (helper NLRs). Sub-functionalized NLRs form a network-type receptor system known as the NLR network. In this review, we highlight the concept of NLR networks, discussing how they are formed, activated, and regulated. Two main types of NLR networks have been described in plants: the ADR1/NRG1 network and the NRC network. In both networks, multiple helper NLRs function as signalling hubs for sensor NLRs and cell surface–localized immune receptors. Additionally, the networks are regulated at the transcriptional and posttranscriptional levels, as well as being modulated by other host proteins to ensure proper network activation and prevent autoimmunity. Plant pathogens in turn have converged on suppressing NLR networks, thereby facilitating infection and disease. Understanding the NLR immune system at the network level could inform future breeding programs by highlighting the appropriate genetic combinations of immunoreceptors to use while avoiding deleterious autoimmunity and suppression by pathogens.

An atypical NLR protein modulates the NRC immune receptor network in Nicotiana benthamiana

“…Plant-pathogen coevolution has driven NLRs to form immune receptor networks [ 25 , 27 ]. The emerging paradigm in the field of plant immunity is that helper NLRs, NRCs, as well as the RESISTANCE TO POWDERY MILDEW 8 (RPW8)-type CC-NLRs (CC R -NLRs) ADR1 and N REQUIREMENT GENE 1 (NRG1), form receptor networks with multiple sensor NLRs [ 54 ]. These genetically dispersed NLR networks are likely to cause a heightened risk of autoimmunity during plant growth and development.…”

NLRX1 increases human retinal pigment epithelial autophagy and reduces H2O2-induced oxidative stress and inflammation by suppressing FUNDC1 phosphorylation and NLRP3 activation

“…The nucleotide-binding oligomerization domain (NOD)like receptor (NLR) family covers evolutionarily conserved constituents of the immune system and exercises crucial roles in inflammation and immune defense. 7 NOD-like receptor X1 (NLRX1) is a unique member of NLR family that negatively modulates the expression level of pro-inflammatory factors and serves the role of inflammasome. 8,9 In addition, NLRX1 has been demonstrated to participate in diverse pathological progresses because of its wide variety of biological functions, such as apoptosis, autophagy, modulation of mitochondrial injury, regulation of reactive oxygen species (ROS) generation, negative modulation of signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), c-Jun N-terminal Kinase (JNK), and interferon-1 (IFN-1).…”

An Overview of PRR- and NLR-Mediated Immunities: Conserved Signaling Components across the Plant Kingdom That Communicate Both Pathways

“…Two major types of plant NLRs have been identified: those that function as direct or indirect sensors of pathogen effectors (TNL and CNL members) and those that act as NLR helpers (RNL members) ( Figure 3 B). Recognition of effectors by plant NLRs follows multiple mechanistic models (direct, guard, decoy, and integrated decoy) described elsewhere [ 24 , 25 , 82 ] and is beyond the scope of this review. Briefly, when NLRs work as singletons, these recognize microbial effectors directly or indirectly and trigger downstream immune responses, behaving both as a sensor and as a signal inducer ( Figure 3 B).…”

“…It has been speculated that TNLs transduce their signal via ADR1s, as well as NRG1s, likely to provide resilience against interference by effectors [ 115 ]. In addition, the finding that ADR1 mediates the biosynthesis of salicylic acid (SA) biosynthesis downstream of RPS2, but independent of its oligomerization capacity, reveals that ADR1 works beyond its function as a calcium channel [ 82 ].…”